Effect of sensory denervation with capsaicin on liver fibrosis induced by common bile duct ligation in rat.
Hepatic fibrosis represents an important stage in the progression of chronic liver disease to cirrhosis. In the present paper we have investigated whether capsaicin-sensitive neuropeptide-containing sensory neurons may participate in the development of liver fibrosis. The expression of hepatic fibrosis induced by common bile duct obstruction has been studied both in capsaicin- and vehicle-treated rats. Common bile duct-induced liver fibrosis was less marked in capsaicin-treated rats than in vehicle-treated rats. Diffuse alterations of liver parenchyma structure with marked collagen deposition and nodular regeneration occurred 8 weeks after common bile duct ligation in vehicle-treated animals, while none of the capsaicin-treated rats exhibited the formation of complete connective septa altering the parenchyma architecture. Both vehicle- and capsaicin-treated rats showed an increasing number of desmin-positive cells in the perivenular zone, but the density of these cells was lower in treated animals than in untreated rats. The hydroxyproline content of the liver increased after common bile duct ligation in a time-dependent manner. Eight weeks after bile duct obstruction vehicle-treated rats showed a 7-fold increase of liver collagen content in comparison to normal animals. This enhancement was about 3.5-fold in capsaicin-treated rats. These findings raise the possibility that the peripheral release of neuropeptides stored in sensory nerves might participate in the development of liver fibrosis following common bile duct obstruction.
Casini
A
A
Department of Pathophysiology, University of Florence, Italy.
Lippe
I T
IT
Evangelista
S
S
Geppetti
P
P
Santicioli
P
P
Urso
C
C
Paglierani
M
M
Maggi
C A
CA
Surrenti
C
C
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D003135:Common Bile Duct / Q000502:physiology / Q000601:surgery*; D003714:Denervation; D003893:Desmin / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006909:Hydroxyproline / Q000032:analysis / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D003893:Desmin; D009479:Neuropeptides; D003094:Collagen; D006909:Hydroxyproline; D002211:Capsaicin